PMID- 19490821
OWN - NLM
STAT- MEDLINE
DCOM- 20090812
LR  - 20211020
IS  - 1539-0829 (Electronic)
IS  - 1534-4827 (Linking)
VI  - 9
IP  - 3
DP  - 2009 Jun
TI  - Lessons learned from studying families genetically predisposed to type 2 diabetes 
      mellitus.
PG  - 200-7
AB  - Early interventions to prevent type 2 diabetes mellitus (T2DM) demand a better 
      understanding of its underlying mechanisms. Nonobese healthy subjects with a 
      strong family history of T2DM (FH(+) subjects) hold a key to this end by allowing 
      the study of the disease before the development of confounding factors, such as 
      obesity or hyperglycemia. In this article, we share our experience over the past 
      decade in studying FH(+) subjects and how lipotoxicity alters glucose metabolism 
      in such individuals, in particular pancreatic beta-cell function. FH(+) subjects 
      have no obvious clinical abnormalities, but when carefully studied, reveal severe 
      hepatic/muscle/adipose tissue insulin resistance and subtle defects in beta-cell 
      function. In most subjects, metabolic adaption allows freedom from diabetes for 
      decades. However, the obesity epidemic is drastically changing this. Given the 
      unique susceptibility of pancreatic beta cells to free fatty acids in FH(+) 
      subjects, interventions that protect against obesity-induced lipotoxicity may 
      hold the greatest promise for preventing T2DM in genetically predisposed 
      individuals.
FAU - Cusi, Kenneth
AU  - Cusi K
AD  - Diabetes Division, Department of Medicine, The University of Texas Health Science 
      Center at San Antonio, San Antonio, TX 78229, USA. cusi@uthscsa.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - United States
TA  - Curr Diab Rep
JT  - Current diabetes reports
JID - 101093791
SB  - IM
MH  - Diabetes Mellitus, Type 2/*genetics/*metabolism
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Insulin Resistance/physiology
MH  - Insulin-Secreting Cells/metabolism/pathology
MH  - Liver/metabolism/pathology
MH  - Muscles/metabolism/pathology
RF  - 50
EDAT- 2009/06/06 09:00
MHDA- 2009/08/13 09:00
CRDT- 2009/06/04 09:00
PHST- 2009/06/04 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/08/13 09:00 [medline]
AID - 10.1007/s11892-009-0033-6 [doi]
PST - ppublish
SO  - Curr Diab Rep. 2009 Jun;9(3):200-7. doi: 10.1007/s11892-009-0033-6.